Calcificaton in blood pumps is a frequent complicaton regardless of the material and the animal species. The precise pathogenesis of pump calcification is not known. In the past 8 years we have studied this phenomenon in over 50 pumps lined with smooth gelatin, rough polyester flock or powdered metal and 200 tissue valve implantations, and we were the one of the first groups to publish findings of calcification in blood pumps. As a result of these studies, we hypothesize that calcification of cardiovascular implants, regardless of whether on smooth or rough surfaces, and whether on moving or non-moving regions, occurs with the same mechanism. The mechanism is dystrophic calcification occurring secondarily in degenerating cellular deposit. The specific aim of this project is to verify this hypothesis and to identify and characterize the nature and the time course of the calcifying process on the smooth polyurethane (Biomer) surfaces currently widely used by other groups in blood pumps. It is still not known whether calcificaton occurs directly on or in the polymer or if it is of the same mechanism as seen in other types of surfaces. In Phase 1, in vitro studies are designed to prove that the degraded blood cells can be the nidi for calcification. Various degraded blood cells are embedded in a gelatin layer and exposed to calcifying solution or plasma with physiological calcium and phosphorus levels. Effects of various lipids levels on calcification also will be tested. The initial calcification loci and their relation to cellular elements are searched for using histochemistry, electron microscopy (EM), x-ray microanalysis (EDX), electron diffraction (ED) and x-ray diffraction (XRD). Quantitation of calcium uptake by the cells will be performed using plasma ashing and atomic adsorption spectrophotometry. In Phase II in vivo study, 12 pusher plate type LVADs lined with a smooth Biomer surface will be implanted in calves for 2 weeks to 4 months. The surfaces of the explanted pumps will be studied by the same technique mentioned above. We also propose to expand our prior tissue valve calcification studies. The elucidation of the pathogenesis of calcification in blood pumps will also be beneficial in understading the mechanism of tissue valve calcification in young patients and of calicfying artherosclerosis.